The broad objective of the project is to understand the actions of the various steroid (androgens, estrogens, glucocorticoids) and peptide hormones (IH FSH, prolactin) and how these actions are mediated. Two models of steroid resistance are under current study: the new world primate, and a family of glucocorticoid resistant men. The new world primates have been found to be resistant to glucocorticoids, estrogens, and progesterone on a receptor mediated basis. The biochemistry of this resistance is being examined. The glucocorticoid resistance in men is also on a receptor mediated basis. The patterns of receptor activation of the two models, however, suggest different underlying defects. The mechanism of prolactin induced hypogonadotropic hypogonadism is also under study. The mechanism by which prolactin regulates IH and FSH selection is being studied in vivo in man and in vitro using a perifusion system. The direct effect of prolactin on th steroid secreting organs (adrenal and gonad) is also being examined by measuring the effects of increased prolactin on steroid biosynthetic activity.